Myxococcus xanthus is a Gram negative bacterium which undergoes a simple cycle of multicellular development. It is an experimentally attractive organism in which to study the role of cell-cell interactions in the regulation of gene expression. The obligatory involvement of intercellular communication during its developmental program is implicated by the behavior of several developmentally defective mutants. The research described in this proposal will focus on one group of mutants, bsgA, which are defective in one of the required cell-cell interactions occuring early in development. The primary defect is loss of an essential protease. As a result of the protease defect, these strains a) produce an extracellular, diffusible molecule which acts as an inhibitor of developmental gene expression by the mutant cells or by neighboring wild-type cells, and b) fail to transcribe any of the known developmentally induced genes. The first objective of this study is to understand the nature of this inhibitory signal; specifically: 1) to identify this inhibitory molecule, 2) to identify the genes required for its synthesis, degradation and interaction with cells, 3) to understand the role of this inhibitor in the development of wild-type cells. The second objective of this study is to understand the mechanism by which the defect in proteolysis affects a) production and/or degradation of the inhibitory factor, and b) developmental gene transcription. The long range goal of this project is to understand the means by which this organism coordinates the behavior of individual cells during multicellular activities. The problem of multicellular coordination is a fundamental problem in developmental biology. The information provided by this work bay help to provide a framework for thinking about tissue interactions in more complex organisms. In this way it is hoped that this work may help us to understand situations in which intercellular coordination goes awry; situations which may in part lead to tragedies such as birth defects and malignancies.